Cell membrane wounding is a disruption of the plasma membrane of cells, and is generally a survivable event. Cell membrane wounding is a common occurrence in mechanically active mammalian tissues such as the endothelial lining of the aorta or gastrointestinal tract, skin epithelia or myocytes of cardiac or skeletal muscle, and has also been demonstrated during the invasion of cells by trypanosomes. In the laboratory setting, cell wounding is typically induced using mechanical means to tear the cell membrane, such as using a microneedle to penetrate the plasma membrane or by scratching a culture dish to sever a portion of a cell.
For large disruptions, such as >1 μm tears in the membrane, a rapid resealing response is required to repair the membrane and maintain cell viability. Initially thought to be a passive process, resealing is now recognized to be an energy and calcium dependent process, resulting in calcium dependent exocytotic vesicle-vesicle and plasma membrane-vesicle fusions that patch the membrane tear. The vesicles sacrificed to provide the membrane patch are now known to be lysosomes. Internal lysosomal membrane is thus added to the cell surface to seal the disruption site. See McNeil, P. L. (2002) J. Cell Sci. 115(5):873; Togo, T., et al. (1999) J. Cell Sci. 112:719; McNeil, P. L., and R. A. Steinhardt (2003) Ann. Rev. Cell Dev. Biol. 19:697.
The repair process appears to require actin depolymerization in order to allow access of the lysosomes to the plasma membrane. In addition, myosin and/or kinesin mediated contractile processes are thought to be involved in bringing the lysosomes into the proximity of the tear. In addition, it is known that subsequent resealing events occur more rapidly than the initial response to the wound, presumably by the increased production of lysosomes from the Golgi. Thus resealing of large disruptions is dependent on functional actin and the Golgi complex to facilitate assess of lysosomes to the wound site, and to reestablish stores of lysosomes to participate in the repair process.
Thus, although cell membrane wounding and subsequent repair is known in the art, there is no teaching or suggestion of inducing cell membrane wounding as a research tool or a therapeutic approach, for example, to permeabilize cells to active agents, or to kill malignant cells. Further, the possibility of using an agent that binds to a cell surface antigen to induce cell membrane wounding has not been suggested. Finally, there is no suggestion of inducing cell membrane wounding using an antibody to treat a disease or disorder in a human or animal patient.